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The increasing number of multi-drug resistant microbial pathogens severely threatens public health worldwide. Antibiotic-resistant pathogenic bacteria, in particular, present a significant challenge. Therefore, there is an urgent need to identify new potential antimicrobial targets and discover new chemical entities that can potentially reverse bacterial resistance. The main goal of this research work was to create and develop a library of 3,6-disubstituted xanthones based on twin drugs and molecular extension approaches to inhibit the activity of efflux pumps. The process involved synthesizing 3,6-diaminoxanthones through the reaction of 9-oxo-9H-xanthene-3,6-diyl bis(trifluoromethanesulfonate) with various primary and secondary amines. The resulting 3,6-disubstituted xanthone derivatives were then tested for their in vitro antimicrobial properties against a range of pathogenic strains and their efficacy in inhibiting the activity of efflux pumps, biofilm formation, and quorum-sensing. Several compounds have exhibited effective antibacterial properties against the Gram-positive bacterial species tested. Xanthone 16, in particular, has demonstrated exceptional efficacy with a remarkable MIC of 11 \u00b5M (4 \u00b5g\/mL) against reference strains Staphylococcus aureus ATCC 25923 and Enterococcus faecalis ATCC 29212, and 25 \u00b5M (9 \u00b5g\/mL) against methicillin-resistant S. aureus 272123. Furthermore, some derivatives have shown potential as antibiofilm agents in a crystal violet assay. The ethidium bromide accumulation assay pinpointed certain compounds inhibiting bacterial efflux pumps. The cytotoxic effect of the most promising compounds was examined in mouse fibroblast cell line NIH\/3T3, and two monoamine substituted xanthone derivatives with a hydroxyl substituent did not exhibit any cytotoxicity. Overall, the nature of the substituent was critical in determining the antimicrobial spectra of aminated xanthones.<\/jats:p>","DOI":"10.3390\/ph17020209","type":"journal-article","created":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T03:22:31Z","timestamp":1707189751000},"page":"209","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Antibacterial Potential of Symmetrical Twin-Drug 3,6-Diaminoxanthones"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4077-6060","authenticated-orcid":false,"given":"Diana I. S. 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General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"}]},{"given":"Sidika","family":"Zubarioglu","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry (LQOF), Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"given":"Joana","family":"Freitas-Silva","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"},{"name":"ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8638-5815","authenticated-orcid":false,"given":"Nikoletta","family":"Szemer\u00e9di","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Albert Szent-Gy\u00f6rgyi Health Center and Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, Semmelweis utca 6, 6725 Szeged, Hungary"}]},{"given":"Madalena","family":"Pinto","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry (LQOF), Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2948-5809","authenticated-orcid":false,"given":"Eug\u00e9nia","family":"Pinto","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"},{"name":"Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6115-8811","authenticated-orcid":false,"given":"Paulo","family":"Martins da Costa","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. 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Chem."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Resende, D.I.S.P., Pereira-Terra, P., In\u00e1cio, \u00c2.S., Costa, P.M.d., Pinto, E., Sousa, E., and Pinto, M.M.M. (2018). Lichen Xanthones as Models for New Antifungal Agents. Molecules, 23.","DOI":"10.3390\/molecules23102617"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Resende, D.I.S.P., Pereira-Terra, P., Moreira, J., Freitas-Silva, J., Lemos, A., Gales, L., Pinto, E., de Sousa, M.E., da Costa, P.M., and Pinto, M.M.M. (2020). Synthesis of a Small Library of Nature-Inspired Xanthones and Study of Their Antimicrobial Activity. Molecules, 25.","DOI":"10.3390\/molecules25102405"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Dur\u00e3es, F., Resende, D.I.S.P., Palmeira, A., Szemer\u00e9di, N., Pinto, M.M.M., Spengler, G., and Sousa, E. (2021). Xanthones Active against Multidrug Resistance and Virulence Mechanisms of Bacteria. Antibiotics, 10.","DOI":"10.3390\/antibiotics10050600"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Vestby, L.K., Gr\u00f8nseth, T., Simm, R., and Nesse, L.L. (2020). Bacterial Biofilm and its Role in the Pathogenesis of Disease. Antibiotics, 9.","DOI":"10.3390\/antibiotics9020059"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1093\/jac\/dky042","article-title":"Role of Bacterial Efflux Pumps in Biofilm Formation","volume":"73","author":"Alav","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Wu, L., and Luo, Y. (2021). Bacterial Quorum-Sensing Systems and Their Role in Intestinal Bacteria-Host Crosstalk. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.611413"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4375","DOI":"10.1016\/j.bmc.2015.06.034","article-title":"The Twin Drug Approach for Novel Nicotinic Acetylcholine Receptor Ligands","volume":"23","author":"Tomassoli","year":"2015","journal-title":"Bioorganic Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1248\/cpb.c14-00017","article-title":"Synthesis of New 5-Substituted Hydantoins and Symmetrical Twin-Drug Type Hydantoin Derivatives","volume":"62","author":"Fujisaki","year":"2014","journal-title":"Chem. Pharm. Bull."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5687","DOI":"10.1073\/pnas.1114944109","article-title":"Transport of Drugs by the Multidrug Transporter Acrb Involves an Access and a Deep Binding Pocket That Are Separated by a Switch-Loop","volume":"109","author":"Eicher","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/nature13205","article-title":"Structure of the Acrab\u2013Tolc Multidrug Efflux Pump","volume":"509","author":"Du","year":"2014","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.resmic.2017.11.001","article-title":"The Hydrophobic Trap\u2014The Achilles Heel of Rnd Efflux Pumps","volume":"169","author":"Aron","year":"2018","journal-title":"Res. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Rosa, G.P., Palmeira, A., Resende, D.I.S.P., Almeida, I.F., Kane-Pag\u00e8s, A., Barreto, M.C., Sousa, E., and Pinto, M.M.M. (2021). Xanthones for Melanogenesis Inhibition: Molecular Docking and Qsar Studies to Understand Their Anti-Tyrosinase Activity. Bioorganic Med. Chem., 29.","DOI":"10.1016\/j.bmc.2020.115873"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8711","DOI":"10.1021\/jo800902j","article-title":"Synthesis and Spectroscopic Properties of Rosamines with Cyclic Amine Substituents","volume":"73","author":"Wu","year":"2008","journal-title":"J. Org. Chem."},{"key":"ref_23","unstructured":"Dax, S., DeCorte, B., Liu, L., McDonnell, M., and McNally, J. (2009). Tricyclic-Bridged Piperidinylidene Derivatives as \u03b4-Opioid Modulators. (7553850B2), U.S. Patent."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Dur\u00e3es, F., Cravo, S., Freitas-Silva, J., Szemer\u00e9di, N., Martins-da-Costa, P., Pinto, E., Tiritan, M.E., Spengler, G., Fernandes, C., and Sousa, E. (2021). Enantioselectivity of Chiral Derivatives of Xanthones in Virulence Effects of Resistant Bacteria. Pharmaceuticals, 14.","DOI":"10.3390\/ph14111141"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"103790","DOI":"10.1016\/j.micpath.2019.103790","article-title":"Reserpine Attenuates Biofilm Formation and Virulence of Staphylococcus Aureus","volume":"138","author":"Parai","year":"2020","journal-title":"Microb. Pathog."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.ijbiomac.2021.08.199","article-title":"Focused Review on Dual Inhibition of Quorum Sensing and Efflux Pumps: A Potential Way to Combat Multi Drug Resistant Staphylococcus Aureus Infections","volume":"190","author":"Kaur","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e00908-19","DOI":"10.1128\/AEM.00908-19","article-title":"Efflux Pumps in Chromobacterium Species Increase Antibiotic Resistance and Promote Survival in a Coculture Competition Model","volume":"85","author":"Benomar","year":"2019","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1107\/S0907444998009378","article-title":"Protein Data Bank (Pdb): Database of Three-Dimensional Structural Information of Biological Macromolecules","volume":"54","author":"Sussman","year":"1998","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"Autodock Vina: Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_30","unstructured":"Clinical and Laboratory Standards Institute (2018). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically, Clinical and Laboratory Standards Institute."},{"key":"ref_31","unstructured":"Clinical and Laboratory Standards Institute (2008). Clinical and Laboratory Standards Institute: Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts, Clinical and Laboratory Standards Institute. Approved Standard-CLSI Document M27-A3."},{"key":"ref_32","unstructured":"Clinical and Laboratory Standards Institute (2008). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi, Clinical and Laboratory Standards Institute. Approved Standard\u2014Second Edition. CLSI Document M38-A2."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Gajd\u00e1cs, M., and Spengler, G. (2019). The Role of Drug Repurposing in the Development of Novel Antimicrobial Drugs: Non-Antibiotic Pharmacological Agents as Quorum Sensing-Inhibitors. Antibiotics, 8.","DOI":"10.3390\/antibiotics8040270"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1021\/acs.jnatprod.8b00326","article-title":"Terpenoids from Euphorbia Pedroi as Multidrug-Resistance Reversers","volume":"81","author":"Ferreira","year":"2018","journal-title":"J. Nat. Prod."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1128\/AAC.47.2.719-726.2003","article-title":"Phenothiazines and Thioxanthenes Inhibit Multidrug Efflux Pump Activity in Staphylococcus aureus","volume":"47","year":"2003","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/2\/209\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:55:37Z","timestamp":1760104537000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/2\/209"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,6]]},"references-count":35,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["ph17020209"],"URL":"https:\/\/doi.org\/10.3390\/ph17020209","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,6]]}}}